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{{Short description|Pharmaceutical drug}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| verifiedrevid = 403499707 |
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| verifiedrevid = 458269701 |
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| image = |
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| image = |
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<!--Monoclonal antibody data--> |
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<!-- Monoclonal antibody data --> |
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| type = mab |
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| type = mab |
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| mab_type = mab |
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| mab_type = mab |
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| target = ] protein F |
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| target = ] protein F |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = Synagis |
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| tradename = Synagis |
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| Drugs.com = {{drugs.com|monograph|palivizumab}} |
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| Drugs.com = {{drugs.com|monograph|palivizumab}} |
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| MedlinePlus = a698034 |
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| MedlinePlus = a698034 |
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| licence_EU = yes |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| DailyMedID = Palivizumab |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = C |
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| pregnancy_AU = |
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| pregnancy_category = |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| routes_of_administration = ] |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| ATC_prefix = J06 |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_status = |
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| ATC_suffix = BD01 |
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| ATC_supplemental = |
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| routes_of_administration = ] |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref>https://www.tga.gov.au/resources/artg/231139 {{Bare URL inline|date=August 2024}}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = <ref name="Synagis SmPC">{{cite web | title=Synagis 100 mg/ml solution for injection - Summary of Product Characteristics (SmPC) | website=(emc) | date=12 August 2020 | url=https://www.medicines.org.uk/emc/product/6963/smpc | access-date=20 August 2020}}</ref> |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Synagis FDA label">{{cite web | title=Synagis- palivizumab injection, solution | website=DailyMed | date=12 May 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e35c4c8-bf56-458f-a73c-8f5733829788 | access-date=20 August 2020}}</ref> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Synagis EPAR" /> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = Rx-only |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = |
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| protein_bound = |
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| metabolism = |
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| metabolism = |
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| metabolites = |
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| onset = |
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| elimination_half-life = 18-20 days |
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| elimination_half-life = 18-20 days |
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| excretion = |
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| duration_of_action = |
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| excretion = |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = NA |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 188039-54-5 |
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| CAS_number = 188039-54-5 |
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| ATC_prefix = J06 |
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| PubChem = |
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| IUPHAR_ligand = |
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| ATC_suffix = BB16 |
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| ATC_supplemental = |
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| PubChem = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00110 |
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| DrugBank = DB00110 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = none |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = DQ448MW7KS |
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| UNII = DQ448MW7KS |
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| KEGG_Ref = |
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| KEGG = D02737 |
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| ChEBI_Ref = |
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| ChEBI = |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201586 --> |
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| ChEMBL = 1201586 |
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| NIAID_ChemDB = |
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| chemical_formula = |
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| PDB_ligand = |
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| synonyms = |
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<!-- Chemical data --> |
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| molecular_weight = |
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| C=6470 | H=10056 | N=1700 | O=2008 | S=50 |
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}} |
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}} |
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'''Palivizumab''' (brand name '''Synagis''' which is manufactured by ]) is a ] produced by recombinant DNA technology. It is used in the prevention of ] (RSV) infections. It is recommended for infants that are high-risk because of prematurity or other medical problems such as congenital heart disease. |
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'''Palivizumab''', sold under the brand name '''Synagis''', is a ] produced by ] technology used to prevent severe disease caused by ] (RSV) infections.<ref name="Synagis SmPC" /><ref name="Synagis EPAR" /> It is recommended for infants at high-risk for RSV due to conditions such as ] or other medical problems including heart or lung diseases.<ref name="Synagis SmPC" /><ref name="Synagis EPAR" /> |
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The most common side effects include ] and ].<ref name="Synagis SmPC" /><ref name="Synagis EPAR">{{cite web | title=Synagis EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/synagis | access-date=20 August 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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Palivizumab is a humanized monoclonal antibody (IgG) directed against an epitope in the A antigenic site of the F protein of RSV. In two Phase III clinical trials in the pediatric population, palivizumab reduced the risk of hospitalization due to RSV infection by 55% and 45%. Palivizumab is dosed once a month via intramuscular (IM) injection, to be administered throughout the duration of the RSV season.<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/palimed102302LB.pdf</ref> |
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Palivizumab is a ] monoclonal antibody (IgG) directed against an ] in the A antigenic site of the F protein of RSV. In two ] in the pediatric population, palivizumab reduced the risk of hospitalization due to RSV infection by 55% and 45%.<ref>{{Cite journal|date=2021|title=Prospective Study for the Use of Palivizumab (Synagis®) in High-risk Children in Germany|url=https://clinicaltrials.gov/ct2/show/NCT01155193 |website=ClinicalTrials.gov}}</ref> Palivizumab is dosed once a month via ], to be administered throughout the duration of the RSV season, which in based on past trends has started in Mid-September to Mid-November.<ref name="Synagis SmPC" /><ref>{{cite journal | vauthors = Borchers AT, Chang C, Gershwin ME, Gershwin LJ | title = Respiratory syncytial virus--a comprehensive review | journal = Clinical Reviews in Allergy & Immunology | volume = 45 | issue = 3 | pages = 331–379 | date = December 2013 | pmid = 23575961 | pmc = 7090643 | doi = 10.1007/s12016-013-8368-9 }}</ref><ref>{{Cite web|last=CDC|date=2020-12-18|title=Trends and Surveillance for RSV in the US.|url=https://www.cdc.gov/rsv/research/us-surveillance.html|access-date=2021-08-10|website=Centers for Disease Control and Prevention|language=en-us}}</ref> |
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Palivizumab targets the fusion protein of RSV,<ref>Levinson, Wilson. "Medical Microbiology and Immunology, 8th ed." Lange: 2004. p. 430.</ref> inhibiting its entry into the cell and thereby preventing infection. |
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Palivizumab targets the fusion protein of RSV,<ref>{{cite book | vauthors = Levinson W | title = Medical Microbiology and Immunology | url = https://archive.org/details/medicalmicrobiol00warr_0 | url-access = registration | edition = 8th | publisher = Lange | date = 2004 | page = | isbn = 9780071431996 }}</ref> inhibiting its entry into the cell and thereby preventing infection. Palivizumab was approved for medical use in 1998.<ref>{{cite book | vauthors = Long SS, Pickering LK, Prober CG |title=Principles and Practice of Pediatric Infectious Disease |date=2012 |publisher=Elsevier Health Sciences |isbn=978-1437727029 |page=1502 |url=https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}}</ref> |
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== Recommendations for use == |
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== Medical use== |
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The ] (AAP) has published recommendations for the use of palivizumab<ref>American Academy of Pediatrics. "Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed." pp 562-565.</ref> Updated AAP recommendations were published in 2009.<ref>American Academy of Pediatrics. "Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed." pp 562-569.</ref> Palivizumab (brand name Synagis manufactured by MedImmune) is used only for prevention, not for treatment, and once initiated for a given RSV season (usually November–March), it should be continued for the full duration of that season. |
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Palivizumab is indicated for the prevention of serious lower respiratory tract disease requiring hospitalization caused by the respiratory syncytial virus (RSV) in children at high risk for RSV disease:<ref name="Synagis SmPC" /><ref name="Synagis EPAR" /><ref>{{cite journal | vauthors = Santos da Silva GN, Monti Atik D, Antunes Fernandes JL, de Freitas do Nascimento D, Fazolo T, Duarte de Souza AP, Baggio Gnoatto SC | title = Synthesis of three triterpene series and their activity against respiratory syncytial virus | journal = Archiv der Pharmazie | volume = 351 | issue = 8 | pages = e1800108 | date = July 2018 | pmid = 29999539 | doi = 10.1002/ardp.201800108 | hdl-access = free | s2cid = 51621538 | hdl = 10923/21468 }}</ref> |
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* children born at 35 weeks of gestation or less and less than six months of age at the onset of the RSV season;<ref name="Synagis EPAR" /> |
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* children less than two years of age and requiring treatment for ] within the last six months;<ref name="Synagis EPAR" /> |
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* children less than two years of age and with hemodynamically significant congenital heart disease.<ref name="Synagis EPAR" /> |
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The ] has published guidelines for the use of palivizumab. The most recent updates to these recommendations are based on new information regarding RSV seasonality, palivizumab pharmacokinetics, the incidence of ] hospitalizations, the effect of ] and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of ] on wheezing, and palivizumab-resistant RSV isolates.<ref name="2014 Pediatrics">{{cite journal | vauthors = Brady MT, Byington CL, Davies HD, Edwards KM, Jackson MA, Maldonado YA, Murray DL, Orenstein WA, Rathore MH, Sawyer MH, Schutze GE | title = Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection | journal = Pediatrics | volume = 134 | issue = 2 | pages = 415–420 | date = August 2014 | pmid = 25070315 | doi = 10.1542/peds.2014-1665 | collaboration = American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. | doi-access = free }}</ref> |
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Reasons to consider palivizumab prophylaxis include: |
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=== RSV Prophylaxis === |
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:''']''' |
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All infants younger than one year who were born at <29 weeks (i.e. ≤28 weeks, 6 days) of gestation are recommended to use palivizumab. Infants younger than one year with ] (i.e. who were born at <32 weeks gestation and required supplemental oxygen for the first 28 days after birth) and infants younger than two years with ] who require medical therapy (e.g. supplemental oxygen, ], diuretics) within six months of the anticipated RSV season are recommended to use palivizumab as prophylaxis.<ref name="2014 Pediatrics" /> Taking palivizumab prophylactically decreases the number of RSV infections, decreases wheezing, and may decrease the rate of hospitalization attributed to RSV.<ref>{{cite journal | vauthors = Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B | title = Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006602 | date = April 2013 | pmid = 23633336 | doi = 10.1002/14651858.cd006602.pub4 }}</ref><ref name="Garegnani_2021">{{cite journal | vauthors = Garegnani L, Styrmisdóttir L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV | title = Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 11 | pages = CD013757 | date = November 2021 | pmid = 34783356 | pmc = 8594174 | doi = 10.1002/14651858.CD013757.pub2 | collaboration = Cochrane Acute Respiratory Infections Group }}</ref> There are few negative side effects reported.<ref name="Garegnani_2021" /> It is not clear if palivizumab is effective and safe for the other medical conditions that put them at a higher risk for serious cases of RSV such as deficiencies in their immune system.<ref name="Garegnani_2021" /> |
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::*≤ 28 weeks gestation and < 12 months of age at the start of RSV season |
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::*29-32 weeks gestation and < 6 months of age at the start of RSV season |
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::*32-35 weeks gestation and < 3 months of age at the start of RSV season, if there is a risk factor (child care attendance or sibling younger than 5 years old) |
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Since the risk of RSV decreases after the first year following birth, the use of palivizumab for children more than 12 months of age is generally not recommended with the exception of premature infants who need supplemental oxygen, bronchodilator therapy, or ] at the time of their second RSV season.<ref name="2014 Pediatrics" /> |
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:''']''' |
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::*Chronic lung disease still requiring oxygen/medication, for the first and second RSV seasons |
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::*Chronic lung disease that required oxygen/medication within the 6 months preceding RSV season, for the first RSV season |
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==== RSV Prophylaxis Target Groups ==== |
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:''']''' |
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* Infants younger than one year of age with ] significant ]. |
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::*Cyanotic heart disease, for the first 24 months of life |
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* Infants younger than one year of age with ] impairing the ability to clear secretions from the upper ] or ]. |
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::*Moderate to severe pulmonary hypertension, for the first 24 months of life |
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* Children younger than two years of age who are ] (e.g. those with severe combined immunodeficiency; those younger than two years of age who have undergone ] or hematopoietic stem cell transplantation) during the ] season. |
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::*Congestive heart failure requiring medication, for the first 24 months of life |
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* Children with ] who have additional risk factors for lower ]s such as congenital heart disease, chronic lung disease, or premature birth.<ref name="2014 Pediatrics" /> |
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::*Children who have undergone open heart surgery during RSV season, for one additional dose after ] (only if they still meet one of the other criteria) |
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* Alaska Native and American Indian infants. |
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Decisions regarding palivizumab prophylaxis for children in these groups should be made on a case-by-case basis.<ref name="2014 Pediatrics" /> |
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=== RSV Treatment === |
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Other conditions where prophylaxis might be considered but inadequate data is available: |
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Because palivizumab is a passive antibody, it is ineffective in the treatment of RSV infection, and its administration is not recommended for this indication.<ref name="2014 Pediatrics" /> A 2019 (updated in 2023) Cochrane review found no differences in palivizumab and placebo on outcomes of mortality, length of hospital stay, and adverse events in infants and children aged up to 3 years old with RSV.<ref>{{cite journal | vauthors = Sanders SL, Agwan S, Hassan M, Bont LJ, Venekamp RP | title = Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 10 | pages = CD009417 | date = October 2023 | pmid = 37870128 | pmc = 10591280 | doi = 10.1002/14651858.CD009417.pub3 }}</ref> Larger RCTs will be required before palivizumab can be recommended as a treatment option.<ref>{{cite journal | vauthors = Hu J, Robinson JL | title = Treatment of respiratory syncytial virus with palivizumab: a systematic review | journal = World Journal of Pediatrics | volume = 6 | issue = 4 | pages = 296–300 | date = November 2010 | pmid = 21080142 | doi = 10.1007/s12519-010-0230-z | s2cid = 22504710 }}</ref> If an infant has an RSV infection despite the use of palivizumab during the RSV season, monthly doses of palivizumab may be discontinued for the rest of the RSV season due to the low risk of re-hospitalization.<ref name="2014 Pediatrics" /> Current studies are in progress to determine new treatments for RSV rather than solely prophylaxis. <ref>{{cite journal | vauthors = Ferla S, Manganaro R, Benato S, Paulissen J, Neyts J, Jochmans D, Brancale A, Bassetto M | title = Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein | journal = Bioorganic & Medicinal Chemistry | volume = 28 | issue = 8 | pages = 115401 | date = April 2020 | pmid = 32143992 | doi = 10.1016/j.bmc.2020.115401 | s2cid = 212622222 | url = https://lirias.kuleuven.be/bitstream/123456789/652873/3/BMC_RSV_2020_main_Accepted.pdf }}</ref> |
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:*] |
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:*] |
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== Contraindications == |
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Of note, a course of palivizumab is quite expensive, and the above recommendations were written based on estimates of its overall cost-effectiveness for preventing severe RSV disease. However, the issues of cost versus benefit remain an area of ongoing research and discussion. |
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Contraindications for the use of palivizumab include hypersensitivity reactions upon exposure to palivizumab. Serious cases of anaphylaxis have been reported after exposure to palivizumab. Signs of hypersensitivity include hives, shortness of breath, hypotension, and unresponsiveness. No other contraindications for palivizumab have been reported.<ref>{{Cite web|title=Drugs@FDA: FDA-Approved Drugs|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103770 |access-date=28 July 2021|website=www.accessdata.fda.gov}}</ref> Further studies are needed to determine if any drug-drug interactions exist as none have been conducted as of yet. |
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==References== |
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== Side effects == |
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Palivizumab use may cause side effects, which include, but are not limited to:<ref>{{cite web|title = Palivizumab Injection | work = MedlinePlus Drug Information|url = https://www.nlm.nih.gov/medlineplus/druginfo/meds/a698034.html| publisher = U.S. National Library of Medicine |access-date = 2016-01-30}}</ref> |
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<references/> |
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* ] |
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* ] |
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* ]s including redness or irritation |
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* ] |
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* ] |
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Some more serious side effects include: |
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* Severe skin ] |
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* ]ing |
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* ] (urticaria) |
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* ] |
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==Pharmacology== |
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=== Pharmacodynamics === |
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Palivizumab has demonstrated a significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV.<ref>{{cite book | vauthors = Wu H, Pfarr DS, Losonsky GA, Kiener PA | chapter = Immunoprophylaxis of RSV Infection: Advancing from RSV-IGIV to Palivizumab and Motavizumab | series = Current Topics in Microbiology and Immunology | title = Human Antibody Therapeutics for Viral Disease | volume = 317 | pages = 103–123 | date = 2008 | pmid = 17990791 | doi = 10.1007/978-3-540-72146-8_4 | isbn = 978-3-540-72144-4 }}</ref> Treatment with 2.5 mg/kg of palivizumab led to a serum concentration of 25-30 μg/mL in cotton rats and reduced RSV titers by 99% in their lungs.<ref name="Resch 2138–2149">{{cite journal | vauthors = Resch B | title = Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection | journal = Human Vaccines & Immunotherapeutics | volume = 13 | issue = 9 | pages = 2138–2149 | date = September 2017 | pmid = 28605249 | pmc = 5612471 | doi = 10.1080/21645515.2017.1337614 }}</ref> |
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==== Mechanism of action ==== |
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Palivizumab is a monoclonal antibody that targets the ] on the surface of RSV, and deactivates it.<ref name="Resch_2017">{{cite journal | vauthors = Resch B | title = Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection | journal = Human Vaccines & Immunotherapeutics | volume = 13 | issue = 9 | pages = 2138–2149 | date = September 2017 | pmid = 28605249 | pmc = 5612471 | doi = 10.1080/21645515.2017.1337614 }}</ref> The F protein is a membrane protein responsible for fusing the virus with its target cell and is highly conserved among subgroups of RSV. Deactivating the F protein prevents the virus from fusing with its target's cell membrane and prevents the virus from entering the host cell.<ref name="Resch_2017" /><ref>{{cite book | vauthors = McLellan JS, Ray WC, Peeples ME | chapter = Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins | series = Current Topics in Microbiology and Immunology | title = Challenges and Opportunities for Respiratory Syncytial Virus Vaccines | volume = 372 | pages = 83–104 | date = 2013 | pmid = 24362685 | pmc = 4211642 | doi = 10.1007/978-3-642-38919-1_4 | isbn = 978-3-642-38918-4 }}</ref> |
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=== Pharmacokinetics === |
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==== Absorption ==== |
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A 2008 meta-analysis found that palivizumab absorption was quicker in the pediatric population compared to adults (''k<sub>a</sub> ='' 1.01/day vs. ''k<sub>a</sub> ='' 0.373/day). The intramuscular bioavailability of this drug is approximately 70% in healthy young adults.<ref name="Robbie_2012">{{cite journal | vauthors = Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK | title = Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children | journal = Antimicrobial Agents and Chemotherapy | volume = 56 | issue = 9 | pages = 4927–4936 | date = September 2012 | pmid = 22802243 | pmc = 3421858 | doi = 10.1128/AAC.06446-11 }}</ref> Current recommendation for RSV immunoprophylaxis is administration of 5 x 15 mg/kg doses of palivizumab to maintain body concentrations above 40 μg/mL.<ref>{{cite journal | vauthors = Reuter SE, Evans AM, Ward MB | title = Reducing Palivizumab Dose Requirements Through Rational Dose Regimen Design | journal = CPT: Pharmacometrics & Systems Pharmacology | volume = 8 | issue = 1 | pages = 26–33 | date = January 2019 | pmid = 30426719 | pmc = 6363066 | doi = 10.1002/psp4.12364 }}</ref> |
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==== Distribution ==== |
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The ] is approximately 4.1 liters.<ref name="Robbie_2012" /> |
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==== Clearance ==== |
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Palivizumab has a drug clearance (CL) of approximately 198 ml/day. The half-life of this drug is approximately 20 days with three doses sustaining body concentrations that will last the entire RSV season (5 to 6 months). A 2008 meta-analysis estimated clearance in the pediatric population by considering maturation of CL and body weight which showed a significant reduction compared to adults.<ref name="Robbie_2012" /> |
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==Society and Culture== |
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=== Cost === |
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Palivizumab is a relatively expensive medication, with a 100-mg vial ranging from $904 to $1866.<ref>{{cite journal | vauthors = Mac S, Sumner A, Duchesne-Belanger S, Stirling R, Tunis M, Sander B | title = Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus: A Systematic Review | journal = Pediatrics | volume = 143 | issue = 5 | pages = e20184064 | date = May 2019 | pmid = 31040196 | doi = 10.1542/peds.2018-4064 | doi-access = free }}</ref> Multiple studies done by both the manufacturer and independent researchers to determine the cost-effectiveness of palivizumab have found conflicting results. The heterogeneity between these studies makes them difficult to compare. Given that there is no consensus about the cost-effectiveness of palivizumab, usage largely depends on the location of care and individual risk factors.<ref>{{cite journal | vauthors = Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B | title = Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006602 | date = April 2013 | pmid = 23633336 | doi = 10.1002/14651858.cd006602.pub4 }}</ref><ref name="Resch_2017"/><ref>{{cite journal | vauthors = Barr R, Green CA, Sande CJ, Drysdale SB | title = Respiratory syncytial virus: diagnosis, prevention and management | journal = Therapeutic Advances in Infectious Disease | volume = 6 | pages = 2049936119865798 | date = 2019-07-29 | pmid = 31384456 | pmc = 6664627 | doi = 10.1177/2049936119865798 }}</ref> |
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A 2013 meta-analysis reported that palivizumab prophylaxis was a dominant strategy with an incremental cost-effectiveness ratio of $2,526,203 per ] (QALY). It also showed an ] for preterm infants between $5188 and $791,265 per ], from the payer perspective.<ref>{{cite journal | vauthors = Mac S, Sumner A, Duchesne-Belanger S, Stirling R, Tunis M, Sander B | title = Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus: A Systematic Review | journal = Pediatrics | volume = 143 | issue = 5 | pages = e20184064 | date = May 2019 | pmid = 31040196 | doi = 10.1542/peds.2018-4064 | doi-access = free }}</ref> However, as previously stated, the cost-effectiveness of palivizumab is undecided, and this meta-analysis is only one example of society can benefit from palivizumab prophylaxis. |
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== History == |
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The disease burden of RSV in young infants and its global prevalence have prompted attempts for vaccine development. As of 2019, there was no approved vaccine for RSV prevention.<ref>{{cite book | vauthors = Shafique M, Zahoor MA, Arshad MI, Aslam B, Siddique AB, Rasool AH, Qamar MU, Usman M | chapter =Hurdles in Vaccine Development against Respiratory Syncytial Virus|date=2019-10-30| chapter-url=https://www.intechopen.com/books/the-burden-of-respiratory-syncytial-virus-infection-in-the-young/hurdles-in-vaccine-development-against-respiratory-syncytial-virus| title = The Burden of Respiratory Syncytial Virus Infection in the Young| veditors = Resch B |publisher=IntechOpen|language=en|doi=10.5772/intechopen.87126|isbn=978-1-78984-642-3|access-date=2021-08-03|doi-access=free}}</ref> A formalin-inactivated RSV vaccine (FIRSV) was studied in the 1960s. The immunized children who were exposed to the virus in the community developed an enhanced form of RSV disease presented by ], fever, and ]. This enhanced form of the disease led to 80% hospitalization in the recipients of FIRSV compared to 5% in the control group. Additionally, 2 fatalities occurred among the vaccine recipients upon reinfection in subsequent years.<ref>{{cite journal | vauthors = Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, Parrott RH | title = Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine | journal = American Journal of Epidemiology | volume = 89 | issue = 4 | pages = 422–434 | date = April 1969 | pmid = 4305198 | doi = 10.1093/oxfordjournals.aje.a120955 }}</ref> Subsequent attempts to develop an attenuated live virus vaccine with optimal ] and minimal ] have been unsuccessful.<ref name="pmid24362694">{{cite book | vauthors = Karron RA, Buchholz UJ, Collins PL | chapter = Live-Attenuated Respiratory Syncytial Virus Vaccines | series = Current Topics in Microbiology and Immunology | title = Challenges and Opportunities for Respiratory Syncytial Virus Vaccines | volume = 372 | pages = 259–284 | date = 2013 | pmid = 24362694 | pmc = 4794267 | doi = 10.1007/978-3-642-38919-1_13 | publisher = Springer Berlin Heidelberg | isbn = 978-3-642-38918-4 | veditors = Anderson L, Graham BS | place = Berlin, Heidelberg }}</ref> Further research on animal subjects suggested that intravenously administered immunoglobulin with high RSV neutralizing activity can protect against RSV infection.<ref>{{cite journal | vauthors = Boukhvalova MS, Yim KC, Blanco J | title = Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus | journal = Antiviral Chemistry & Chemotherapy | volume = 26 | pages = 2040206618770518 | date = 2018-01-01 | pmid = 29768937 | pmc = 5987903 | doi = 10.1177/2040206618770518 }}</ref> In 1995, the ] (FDA) approved the use of RespiGam (RSV-IGIV) for the prevention of serious lower respiratory tract infection caused by RSV in children younger than 24 months of age with ] or a history of ].<ref>{{cite journal | vauthors = Pollack P, Groothuis JR | title = Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV | journal = Journal of Infection and Chemotherapy | volume = 8 | issue = 3 | pages = 201–206 | date = September 2002 | pmid = 12373481 | doi = 10.1007/s10156-002-0178-6 | s2cid = 39331984 }}</ref> The success of the RSV-IGIV demonstrated efficacy in immunoprophylaxis and prompted research into further technologies. Thus, Palivizumab was developed as an antibody that was found to be fifty times more potent than its predecessor. This antibody has been widely used for RSV since 1998 when it was approved.<ref name = "Dessain_2021">{{Cite book |url= https://www.worldcat.org/oclc/209988317 |title=Human antibody therapeutics for viral disease|date=2021|publisher=Springer Verlag| vauthors = Dessain SK |isbn=978-3-540-72146-8|location=Berlin|oclc=209988317}}</ref> |
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Palivizumab, originally known as MEDI-493, was developed as an RSV immune prophylaxis tool that was easier to administer and more effective than the current tools of that time (the 1990s).<ref name = "Dessain_2021" /> It was developed over a 10-year period by MedImmune Inc. by combining human and mouse DNA.<ref>{{cite journal | vauthors = Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, Dormitzer M, O'Grady J, Koenig S, Tamura JK, Woods R, Bansal G, Couchenour D, Tsao E, Hall WC, Young JF | title = Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus | journal = The Journal of Infectious Diseases | volume = 176 | issue = 5 | pages = 1215–1224 | date = November 1997 | pmid = 9359721 | doi = 10.1086/514115 | doi-access = free }}</ref> Specifically, antibody production was stimulated in a mouse model following immunization with RSV. The antibody-producing B cells were isolated from the mouse's spleen and fused with mouse myeloma cell lines. The antibodies were then humanized by cloning and sequencing the DNA from both the heavy and light chains of the monoclonal antibody. Overall, the monoclonal antibody is 95% similar to other human antibodies with the other 5% having DNA origins from the original mouse.<ref name="Resch 2138–2149"/> |
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== References == |
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{{Monoclonals for infectious disease and toxins}} |
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